We are in our 8th cholerae pandemic, a disease that infects millions and kills over 100,000 humans annually. In one stage of its life cycle, the infective agent, Vibrio cholerae, lives as a commensal with copepods, a microcrustacean found in drinking water. Because the bacteria "burrow" into the cuticle, they escape the stomach acid barrier, to which free-living cells are sensitive. Thus, the chitinolytic properties of V. cholerae are directly relevant to human health and disease. In previous work with Vibrio furnissii, we found that chitin degradation involves a cascade, with at least three signalling systems and numerous genes and proteins, many of which were isolated. One of these was a sensor HK (histidine kinase) protein, which represents a breakthrough in this research. An in frame deletion of the sensor has a global effect on chitin utilization in that none of the characterized chitin cascade genes or processes were expressed. When the sequence of the V. cholerae genome became available, the predicted protein sequences of genes involved in chitin utilization that we had characterized in V. furnissii exhibited considerable identity to the corresponding ORFs in the V cholerae genome. For example, the V. furnissii sensor is 84% identical and 93% similar to VC0622 over the full length of the predicted protein sequences. The sensor is homologous to the E. coli ArcB sensor, part of a two component signal transduction system. Over 21 ORFs in the V. cholerae genome are annotated as related to chitin catabolism (independent of GlcNAc catabolism). Of these, ten were characterized in V. furnissii but nothing is known about the remainder. We shall determine which genes are regulated by VC0622, using first an in frame deletion of VC0622. A second goal is to isolate and characterize the sensor HK protein from V. cholerae. Finally, we plan to identify and characterize the cognate HPt and RR protein(s) that interact with the sensor. The work will rely heavily on molecular biological and biochemical techniques, as well as genomics.